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Genome-wide DNA methylation analysis

Abstract

Over the past decades it has become ever more apparent that understanding the genome did not stop with unravelling the genetic code. Regulatory mechanisms are needed to determine which parts of the genome are active or inactive, and to form a memory system that can be passed on over multiple cell divisions for proper functioning of the cell. These mechanisms underpinning heritable gene regulation are encapsulated by the term "epigenetics" and include histone modifications, miRNA and non-coding RNA expression, and methylation of cytosine residues in DNA. In this review, we compare the various methods that can be used to analyse DNA methylation patterns throughout the genome, and discuss their advantages and disadvantages. In addition, we present a detailed protocol for genome-wide DNA methylation analysis based on the capture of methylated DNA using a methyl-CpG binding domain-based (MBD) protein combined with second generation sequencing.